Phosphorylation target site specificity for AGC kinases DMPK E and lats2

Abstract

Serine/threonine kinases of the AGC group are important regulators of cell growth and motility. To examine the candidate substrate profile for two members of this group, DMPK E and Lats2, we performed in vitro kinase assays on peptide arrays. Substrate peptides for both kinases exhibited a predominance of basic residues surrounding the phosphorylation target site. 3D homology modeling of the kinase domains of DMPK E and Lats2 indicated that presence of two negative pockets in the peptide binding groove provides an explanation for the substrate preference. These findings will aid future research toward signaling functions of Lats2 and DMPK E within cells.

Kinome Profiling

“…Two early studies, published in Cancer Research, used this platform to characterise the changes in the sequence of cellular events leading to adenocarcinoma of the oesophagus [63–66], whereas the other characterised signalling in colorectal cancer [67, 68], but this platform was also used for charting differences in the substrate specificity of related kinases, for example, to characterise the differences between c-Raf and Cot [69] or the phosphorylation target site of DMPK E and lats2 [70] and thus was the first academically truly successful peptide-array-based kinome profiling tool, used in a variety of species (e.g., Guinea pigs [71]). An important recently published study used this platform to characterise the changes in cellular kinome associated with differentiation during haematopoiesis [72], showing that even under unstimulated conditions important differences between cell stages exist, challenging the notion that cellular signalling is mainly reactive.…”